1. Field of the Invention
The present invention relates to the use of porphyrin-complex and expanded porphyrin-complex compounds for use as a diagnosticum, in particular for use as a diagnosticum for the detection, localization, and monitoring of an infarction, and of a necrosis.
2. Description of the Prior Art
Suitable porphyrin-complex compounds are subject of DE-A-4,232,925, DE-A-4,305,523, EP-A-336,879, and EP-A-355,041. The subject matter of these applications are included by cross reference.
These porphyrin-complex compounds are used as a pharmaceutical preparation for the diagnosis and therapy of tumours.
Other suitable porphyrin-complex compounds are expanded prophyrin-complex compounds (17).
The present invention is based on the insight that these porphyrin-complex compounds can be used for the detection, localization, and monitoring of an infarction, and of a necrosis.
Hereafter the use as an infarction localization diagnosticum is primarily exemplified for a myocardial infarction and for a renal infarction, but it will be obvious for a skilled person that due to similar pathophysiological situations the same experimental findings apply to other infarction such as those of the intestines, lung, brain and the like.
Myocardial infarction is not a stable pathophysiological situation, but instead progresses to its definite form over several weeks to months. This process can be subdivided, although overlapping, in at least three periods. The first 24 hours after the start of ischemia (acute evolving myocardial infarction) damage progresses as a wavefront phenomenon from the subendocardium to include the myocardium transmurally. During the second phase (established myocardial infarction) this area stabilizes and fibrosis is formed as a healing process. The third phase (healed infarction) starts after all the damaged tissue is replaced by a fibrotic scar. During this phase, considerable remodelling takes place. So far no accurate and reliable technique exists that can determine the evolution phase of the myocardial infarction antemortem.
The most important long-term prognostic factor after a myocardial infarction is the amount of myocardial tissue lost during this process. So far, no accurate and reliable technique exists to demonstrate the end-point, the amount of irreversibly damaged tissue antemortem.
In the three phases described above, it is of extreme importance to have an accurate status about the amount and localization of the affected myocardial tissue. During an evolving myocardial infarction, it is important to assess the amount of tissue at risk, the amount already lost, and from these parameters the amount of tissue that can be salvaged by reperfusion by thrombolysis or emergency surgical revascularisation, according to the hemodynamic status of the patient. In a patient with unstable angina, it is often impossible to discriminate between reversibly injured (akinetic, stunned) myocardium and irreversibly damaged tissue. This would nevertheless have a profound impact on the therapeutic strategy. In the case of complications in the phase of established infarction: requiring surgical intervention, it is known that mortality is highest when dead tissue is revascularized, causing hemorrhagic infarctions. An operative strategy of repair of the ventricular septum defect or mitral insufficiency with selective revascularisation of non-necrotic tissue could save lives.
Up to now, a satisfactory in vivo method for localizing and defining an infarction and the size of an infarction has not yet been available, which impedes the progress of both the basic research and clinical practice (1). For instance, current imaging techniques such as echocardiography (2), nuclear scintigraphy with perfusion and infarct avid tracers (3-5) and magnetic resonance imaging (MRI) without and with different contrast media (6-9) are still far from optimal in terms of sensitivity, specificity, spatial resolution, contrast and reliability (3).
Similar contemplations apply for infarctions of the kidney intestines, lung and brain.
Necrosis is a status of local tissue death, and results from the effects of diseases resulting in an adverse and detrimental effect on body tissue. Necrosis may be caused by radiation, injury, chemicals, local oxygen deficiency, infections, cancer, and the like. Monitoring, localization and detection of necrosis allows the follow up and effectiveness determination of all kinds of diagnostic and therapeutic therapies and treatments.